Nitric Acid → N-(3-Fluoro-4-nitrophenyl)acetamide

HRID 1241972Notes

Reaction equation

HRID 1241972 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[NH:5][C:6](=[O:8])[CH3:7].S(=O)(=O)(O)O.[N+:17]([O-])([OH:19])=[O:18].C(Cl)Cl>O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[N+:17]([O-:19])=[O:18])[NH:5][C:6](=[O:8])[CH3:7]

Participants

6

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 9594N-(3-Fluorophenyl)acetamide

Product 1

HCID 2755770N-(3-Fluoro-4-nitrophenyl)acetamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Added 3′-fluoroacetanilide (3.06 g, 20 mmol) cautiously to concentrated sulfuric acid (6 mL) at 5° C. To the resulting solution, added fuming nitric acid (1.05 mL, 25 mmol) dropwise while maintaining temperature at 5–10° C. After 30 min, added ice (50 g), later diluted with water (100 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with saturated NaHCO3 and brine, dried over anhydrous Na2SO4 and concentrated to give the crude product (4.0 g) as a mixture of isomers (1:1.4 ratio of 4′-nitro/2′-nitro). The desired isomer, 3′-flouro-4′-nitroacetanilide, was isolated by flash chromatography (DCM-5% MeOH/DCM) in low yield (1.2 g, 30%) as a yellow solid. 1H-NMR (CDCl3): δ 8.08 (1H, app t), 7.82 (1H, dd), 7.41 (1H, br s), 7.21 (1H, m), 2.25 (3H, s).

Workup

  1. temperaturewhile maintaining temperature at 5–10° C
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined organic layers were washed with saturated NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto give the crude product (4.0 g)
  7. additionas a mixture of isomers (1:1.4 ratio of 4′-nitro/2′-nitro)

Sources & evidence

ORD record
ord-da3f4300b22e40adad5520d73a6d10ec
Source dataset
uspto-grants-2006_10
Patent number
US07115640B2

Reaction notes

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